This application is to study comorbid disorders that affect the treatment of opiate dependence. The specific aims of the proposed program of research are as follows: Study 1 will examine comorbid depression as a predictive factor in treatment with desipramine and contingency management of cocaine abusing opiate dependent subjects maintained on buprenorphine by secondary data analysis of a completed randomized clinical trial. Study 2 will evaluate the efficacy of sertraline in the treatment of cocaine dependent patients with comorbid depression in a recently started double-blind randomized clinical trial. Study 3 will determine changes of health care cost after treatment of opiate dependence in the Veterans Affairs health delivery system using existing administrative databases. It will determine whether confounding factors, especially comorbid depression and cocaine dependence, may affect changes in costs. The overall aim of the proposal is to provide me with a supervised patient oriented research and educational experience that will enable me to become an independent investigator in substance abuse. My specific career development goals are to: (1) Acquire in-depth knowledge of the neuropharmacology of cocaine and opiate dependence, and of substance induced mood disorders. (2) Develop expertise in clinical research and management of cocaine and opiate dependence, and current pharmacotherapies. (3) Develop skills in Mental Health Service research related to substance abuse. The proposed career development plan utilizes the collaboration of Thomas Kosten, MD in developing expertise executing randomized clinical trials, Robert Rosenheck, MD in developing skills in mental health services research and Kevin Sevarino, MD, PhD in clinical management of opiate dependence. The educational experience includes a four year period of formal coursework at the Interdepartmental Neuroscience Program at the Yale School of Medicine and at the Yale School of Epidemiology and Public Health. This K23 research career award will enable me to start an academic career focusing on research in cocaine and opiate dependence and to develop a bridge between clinical trials and services research.